RT Journal Article
T1 The lack of EphB3 receptor prevents bone loss in mouse models of osteoporosis
A1 Rodríguez-Sosa, Mariano R.
A1 Castillo, Luis M. del
A1 Belarra, Adrián
A1 Zapata González, Agustín Gregorio
A1 Alfaro Sánchez, David
AB Bone homeostasis is a complex process in which some Eph kinase receptors and their ephrin ligands appear to be involved. In the present study, we address this issue by examining, both in vitro and in vivo, the role of EphB2 and EphB3 in mesenchymal stromal/stem cell (MSC) differentiation into bone tissue. This was first evaluated by quantitative reverse transcription PCR (RT-qPCR) and histological staining in MSCs cultured in specific mediums revealing that although EphB2-/- MSCs mainly expressed pro-adipogenic transcription factors, EphB3-/- MSCs showed abundant osteogenic transcripts, such as Runx2, Msx2, and Sp7. To clarify the underlying molecular mechanisms, we found that the lack of EphB3 signaling alters the genetic profile of differentiating MSCs, reducing the expression of many inhibitory molecules and antagonists of the BMP signaling pathway, and increasing Bmp7 expression, a robust bone inductor. Then, to confirm the osteogenic role of EphB3 in vivo, we studied the condition of 2 mouse models of induced bone loss (ovariectomy or long-term glucocorticoid treatment). Interestingly, in both models, both WT and EphB2-/- mice equally developed the disease but EphB3-/- mice did not exhibit the typical bone loss, nor an increase in urine Ca2+ or blood serum CTX-1. This phenotype in EphB3-KO mice could be due to their significantly higher proportions of osteoprogenitor cells and preosteoblasts, and their lower number of osteoclasts, as compared with WT and EphB2-KO mice. Thus, we conclude that EphB3 acts as a negative regulator of the osteogenic differentiation, and its absence prevents bone loss in mice subjected to ovariectomy or dexamethasone treatment.
PB Oxford University Press
SN 0884-0431
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/118796
UL https://hdl.handle.net/20.500.14352/118796
LA eng
NO Rodríguez-Sosa, M. R., del Castillo, L. M., Belarra, A., Zapata, A. G., & Alfaro, D. (2024). The lack of EphB3 receptor prevents bone loss in mouse models of osteoporosis. Journal of Bone and Mineral Research, 39(7), 1008-1024. https://doi.org/10.1093/jbmr/zjae075
NO This study was financially supported by the "Instituto de Salud Carlos III" (ISCIII).RD16/0011/0002/Instituto de Salud Carlos IIIRD21/0017/0010/Red de Terapia CelularRed Española de Terapias AvanzadasEuropean Union ProgramNextGenerationEURecovery, Transformation and Resilience PlanS2017/BMD-3692/Madrid Regional GovernmentRTI2018-093938-B-100/Ministry for Science and InnovationRegional Ministry of ScienceUniversities and Innovation of the Community of MadridEuropean Social FundYouth Employment Initiative
NO Instituto de Salud Carlos III
NO European Commission
NO Comunidad de Madrid
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 13 abr 2025